Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans

Abstract

IMPORTANCE The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain. OBJECTIVE To describe the relationship between SCT and CKD and albuminuria in self-identified African Americans. DESIGN, SETTING, AND PARTICIPANTS Using 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987–2013; n = 3402], Jackson Heart Study [JHS, 2000–2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985–2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000–2012; n = 1620], and Women’s Health Initiative [WHI, 1993–2012; n = 8000]), we evaluated 15 975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14 727 participants without SCT [noncarriers]). MAIN OUTCOMES AND MEASURES Primary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model. RESULTS A total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14 722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34–1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%–10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45–2.20]; ARD, 8.5% [95% CI, 5.1%–12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07–1.61]; ARD, 6.1% [95% CI, 1.4%–13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49–2.31]; ARD, 12.6% [95% CI, 7.7%–17.7%]). CONCLUSIONS AND RELEVANCE Among African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans.

Elevated D-dimer levels in African Americans with sickle cell trait

“…In addition, this relationship was independent of baseline eGFR, which is strongly associated with SCT and has been demonstrated to influence D-dimer measurements. 19,20 Although elevated D-dimer levels have long been observed in SCD, the relationship between SCT and D-dimer levels has not been clearly established. Two small case-control studies have shown an association of SCT to D-dimer, but these analyses were limited by sample size and lack of adjustment for confounders.…”

Association among sickle cell trait, fitness, and cardiovascular risk factors in CARDIA

“…Our finding that SCT carriers do not have an increased risk of developing hypertension over the course of 25 years aligns with recent findings by Naik et al, who reported that SCT is associated with an increased risk for incident chronic kidney disease, decline in kidney function over time, and albuminuria in their study of almost 16 000 African American participants from various cardiovascular cohorts, including a subset of CARDIA participants. 16 The authors, however, did not find baseline differences in hypertension by SCT status or that the association between SCT and chronic kidney disease was modified by hypertension. In our analysis, we focused on the relationship of SCT status to hypertension, but not chronic kidney disease, as hypertension is better tied to fitness as a predictor of cardiovascular disease risk.…”

“…We performed single-gene, single-nucleotide polymorphism (SNP) genotyping by functionally tested TaqMan SNP Genotyping Assays in accordance with manufacturer protocols (Life Technologies, Grand Island, NY). Details about assay design and experimental procedures are described in Naik et al 16 We obtained genotype data for SNP rs334 encoding for hemoglobin S trait, otherwise known as SCT, and for SNP rs33930165 encoding for hemoglobin C trait, another common hemoglobin variant. We genotyped for hemoglobin C trait, given the possibility of coinheritance of hemoglobin S and C in some individuals, which results in a clinically significant variant of sickle cell disease.…”

Live Donor Kidney Transplantation Pearls: A Practical Review

“…These include proteinuria and/or haematuria, impaired renal function (defined as GFR <80 mL/min/1.73 m2), markedly abnormal urologic and renal vascular abnormalities, any chronic, active viral infection (human T-lymphotropic virus [HTLV], HBV and HCV), history of malignancy, chronic illness, particularly pulmonary, liver, autoimmune, neurologic, or cardiac disease, clinically significant hypertension, nephrocalcinosis, bilateral kidney stones, or recurrent nephrolithiasis, active substance abuse, pregnancy and disorders requiring anticoagulation [35]. The following are some relative contraindications to living kidney donation.…”